During viral respiratory infections, there is increased airway hyperirritability in asthma. While the mechanism of this increased sensitivity is not established, it is our hypothesis that this occurs, in part, from metabolic changes resulting from viruses or a by-product of virus infected cells. These virus induced changes interfere with the response of a wide variety of cell types including the bronchial sensory neurons making them hyperreactive to opposing stimuli such as cholinergic agonists or histamine. These changes are not limited to the airways and therefore for study, isolated leukocytes have provided in vitro tissue to examine these hcanges. In this proposal we have used the granulocyte for in vtro studies using it as a model to examine changes in modulation of complement activated zymosan particle induced release of lysosomal enzyme by agonists; i.e., isoproterenol, histamine, prostaglandin E1 and F2 and carboachol. Studies with granulocytes have shown a decreased response to isoproterenol in asthma and this is further impaired during viral respiratory infections provoking asthma. In vitro incubation of granulocytes with rhinovirus 16 and influenza viruses have impaired the granulocyte response to agnoists as seen during respiratory infections. We propose to examine and characterize the change in agonist response in the presence of viruses with the granulocyte model and also the lymphocyte cyclic AMP response to the above noted agonists and determine the characteristics of the factor rendering this change. We propose to quantitate the relative change in beta-adrnergic receptors of granulocyte membranes following virus treatmnt. In addition, we intend to study and characterize the effect of virus infections upon the isolated airway smooth muscle response to agonists and the antigen induced release of mediators in guinea pig and post-mortem human smooth muscle.